The prophylactic antiemetic therapies in management of differentiated thyroid cancer patients with radioactive iodine therapy: a single-center, non-randomized clinical trial.

Objective: The present study was to investigate three different single-drug regimens to show which was more effective to reduce radioactive iodine therapy (RAI) associated nausea and vomiting, and to compare the occurrence of long-term gastrointestinal diseases after RAI therapy. Method: We performed a single-center, non-randomized clinical trial among patients who underwent RAI therapy from March 2016 to July 2022. Enrolled patients were divided into four cohorts based on the date of the treatment. cohort 1, with no preventive antiemetics; cohort 2, received 20 mg of pantoprazole per day for 3 days; cohort 3, received a 10 mg metoclopramide tablet two times daily for 3 days; cohort 4, oral ondansetron, 8 mg, twice daily for 3 days. The primary endpoints were proportion of patients who experience vomiting episodes and nausea during the 7-day hospital period. Secondary end points included Functional Living Index Emesis (FLIE) quality-of life questionnaires and the occurrence of gastrointestinal diseases. Results: A total of 1755 patients were analyzed, comprised of 1299 (74.0%) women and 456 (26.0%) men, with a median age of 44 years (range 18-78 years). The characteristics of patient were similar within the four groups. 465 (26.4%) patients developed RAI-associated nausea, and 186 (14.4%) patients developed RAI-associated vomiting. The rate of nausea was significantly decreased in the patients who were taking ondansetron when compared with the other cohorts (P<0.05), while the rate of vomiting (≥6 episodes) was slightly lower. As secondary endpoint, FLIE measures ondansetron scored highly compared to other cohorts, from baseline (mean score of 110.53 ± 17.54) to day 7 (mean score of 105.56 ± 12.48). In addition, 48 (2.7%) patients were found to be with gastrointestinal diseases at the end of one year follow up. Multiple RAI therapy and higher dose of I-131 per body weight revealed a significantly independent risk factors of developing gastrointestinal disorders. Conclusions: In conclusion, the present study demonstrated that short-term ondansetron could be an effective prophylactic agent in controlling RAI-associated nausea and vomiting. Furthermore, the risk of developing gastrointestinal disorders was significantly higher for patients with multiple RAI therapy and higher dose of I-131 per body weight.

Clinical and radiological differentiation between Trousseau syndrome and cardiogenic embolism: a retrospective case-control study.

Background: Trousseau syndrome (TS) is a thromboembolic event in cancer patients caused by abnormalities in coagulation and fibrinolytic mechanisms. Acute multiple cerebral infarction (AMCI) is a rare form of TS. This study aimed to discuss the differentiation of clinical and radiographic characteristics between TS and cardiogenic embolism (CE) with AMCI as the main manifestation. Methods: We retrospectively analyzed 69 patients with TS-AMCI and 105 patients with CE-AMCI who were treated at Shandong Provincial Hospital between August 2018 and October 2022. The clinical baseline data, laboratory indices, and imaging characteristics of the two groups were compared. A logistic regression was used to analyze the risk factors of TS-AMCI, and receiver operating characteristic (ROC) curves were used to analyze the predictive value of the risk factors. Results: In relation to the clinical data, there were statistically significant differences between the two groups of patients in terms of the lipid and coagulation indices. D-dimer [odds ratio (OR) =4.459, 95% confidence interval (CI): 1.871-10.625; P=0.001] and triglyceride (OR =6.001, 95% CI: 2.375-15.165; P<0.001) were independent risk factors for TS-AMCI. In relation to the radiographic characteristics, the infarctions in the TS-AMCI group were widely distributed in multiple arterial supply areas [23 (33.3%) vs. 10 (9.5%); P<0.001]. More importantly, bilateral anterior + posterior circulation was also an independent risk factor for TS-AMCI (OR =15.005, 95% CI: 1.757-128.17; P=0.013). Conclusions: Unexplained AMCI in the cancer-prone age group, abnormalities in the lipid and D-dimer levels, and infarction foci involving multiple arterial blood supply areas suggested a high probability of TS.

BRAF V600E mutation in papillary thyroid microcarcinoma: is it a predictor for the prognosis of patients with intermediate to high recurrence risk?

OBJECTIVE: The BRAFV600E mutation is the universal genetic mutation in papillary thyroid microcarcinoma (PTMC). The present study is to estimate the role of the BRAFV600E mutation in the clinical outcome of PTMC with intermediate to high recurrence risk after radioactive iodine (RAI) therapy, which is considered to be an indolent tumor. METHODS: We conducted a single-center retrospective study. Between May 2016 and March 2019, PTMC patients with known BRAFV600E status who received RAI therapy were reviewed at the Second Hospital of Shandong University. Treatment and follow-up were defined according to criteria used in the 2015 ATA guidelines. The association between the BRAFV600E mutation and clinicopathological characteristics, response to RAI therapy, and recurrence after a period of follow-up were analyzed. Propensity score matching (PSM) and logistic regression were used to control confounding variables. RESULTS: Of the 322 patients with intermediate to high recurrence risk in PTMC, the mean age of the patients were 43.7 ± 12.2 years, and 72.1% were women. BRAFV600E mutation was found in 64.9% (209/322). After PSM, 112 pairs of patients were matched, and except for multifocality (P = 0.001), extrathyroidal invasion (P = 0.003) and tumor size (P = 0.03), there was no significant difference in all baseline characteristics between the two groups. An excellent response (ER) to RAI therapy was observed in 273 patients (84.7%). At the end of the study, 17(5.2%) and 6(1.8%) patients showed structural incomplete response (SIR) and biochemical incomplete response (BIR) status. The proportion of patients who achieved ER status in the BRAFV600E mutation positive and negative groups was 86.6% and 81.4%, respectively. Kaplan-Meier analyses showed that the BRAFV600E mutation was not related to lower ER reached time. The median follow-up was 51 months. CONCLUSIONS: We found the BRAFV600E mutation was associated with multifocality, extrathyroidal invasion, and tumor size in papillary thyroid microcarcinoma. However, the BRAFV600E mutation had no significant association with clinical outcomes in patients with intermediate to high recurrence risk after RAI therapy. Furthermore, the extra-thyroid uptake results and distant metastasis had been proven to be independent factor predicting the clinical response. REGISTRATION NUMBER: ChiCTR2200062911.

The potential association of peripheral inflammatory biomarkers in patients with papillary thyroid cancer before radioiodine therapy to clinical outcomes.

Purpose: Neutrophil-lymphocyte ratio (NLR), markers-lymphocyte-to-monocyte ratio (LMR), and platelet to-lymphocyte ratio (PLR) have potential roles as prognostic biomarkers in various cancers. The study was evaluated to investigate the predictive value of the peripheral inflammatory biomarkers in patients with papillary thyroid carcinoma (PTC) before radioiodine therapy to the response of clinical outcomes. Methods: We retrospectively analyzed the patients diagnosed with PTC at the Second Hospital of Shandong University between September 2018 and January 2020. Patients were divided into low and high inflammatory biomarker groups based on median values. The area under the receiver operating characteristic curves (ROC) and logistic regression were used to explore the potential risk factors. Results: A total of 692 patients were enrolled, which included 197 (28.4%) males and 495 (71.6%) females. The median values of NLR, LMR and PLR of these patients were 1.7 (range 0.3-5.7), 7.1 (range 1.1-23.4) and 137.6 (range 27.6-497.5), respectively, and the mean values were 1.95 ± 0.82, 7.4 ± 2.5 and 148.7 ± 54.8, respectively. Compared to the lower PLR group, the higher group was significantly associated with gender, tumor size, N stage and thyroglobulin level (P<0.05). At the end of follow-up, 75.5% (523/692), 13.3% (91/692), 4.5% (31/692), and 6.7% (47/692) of patients were evaluated as excellent response (ER), indeterminate response (IDR), structural incomplete response (SIR), and biochemical incomplete response (BIR) respectively. In term of clinical outcomes, the NLR, LMR and PLR showed relatively low discriminative power (P≥0.05). Conclusion: We found that higher PLR values was associated with poor clinicopathological features in PTC. However, the peripheral inflammatory indicators (NLR, LMR and PLR) may be insufficient to predict short-term clinical outcomes of patients with radioiodine therapy.

Potential Impact of Body Mass Index on the Clinical Outcome of Papillary Thyroid Cancer After High-Dose Radioactive Iodine Therapy.

Context: Obesity has been reported as a potential risk factor for the aggressiveness of papillary thyroid cancer (PTC), but the data gathered so far are conflicting. Objective: The aim of our study was to evaluate the relationship between body mass index (BMI) and aggressiveness of PTC at the diagnosis and clinical outcome. Methods: A total of 337 patients who underwent radioactive iodine (RAI) therapy between March 2017 and May 2020 were recruited. Patients were divided into four groups: underweight (BMI<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (BMI≥ 30 kg/m2). Treatment and follow-up were defined according to criteria used in the 2015 ATA guidelines. Results: This study included 337 patients with PTC (71.5% women, median age 45.21 ± 13.04 years). The mean BMI was 24.2 ± 3.1 kg/m2. Obese groups had a higher age than the other groups (P = 0.001). Moreover, obese patients had larger tumor sizes and higher T stage, compared to overweight, normal weight, and underweight patients (P = 0.007). After a median follow-up of 32 months, 279 patients (82.7%) had achieved an excellent response (ER) to therapy. The overall ER rates were compared between groups, and they did not differ significantly. Conclusions: We demonstrated that BMI may have an additive effect on the aggressiveness of PTC, but did not have an effect on the response to therapy after high-dose RAI therapy.

The genetic duet of BRAF V600E and TERT promoter mutations predicts the poor curative effect of radioiodine therapy in papillary thyroid cancer.

OBJECTIVE: The BRAF V600E and TERT promoter mutations are well known to be associated with poor clinical outcomes of papillary thyroid cancer (PTC). Radioactive iodide (RAI)-refractory can be evaluated in advance of treatment, for which predictive biomarkers may be helpful. The present study is to analyze the correlation of both mutations with the curative effect of radioiodine therapy. METHODS: A total of 126 patients who underwent RAI therapy from October 2016 to August 2019 were recruited. Treatment and follow-up were defined according to criteria used in the 2015 ATA guidelines. The RAI response of patients was assessed as excellent response (ER) and RAI-refractory at the end of follow-up. RESULTS: When dividing the 126 patients into 4 groups, the no mutation, only BRAF V600E mutation, only TERT promoter mutation, and coexistence of two mutation groups were found in 15.8%, 68.3%, 2.4%, and 13.5% patients. RAI-refractory was found in 52.9% (9/17) patients with the coexisting BRAF and TERT mutations. In logistic regression analysis, M1, BRAF, and TERT mutation were confirmed to be independent factors predicting the RAI-refractory. Moreover, 35.3%, 41.2%, and 23.5% of patients in the BRAF and TERT mutation group were assessed as ER, SIR, and BIR respectively. Kaplan-Meier analyses revealed that the genetic duet of BRAF V600E and TERT promoter mutations was associated with a lower ER reached time. CONCLUSIONS: We found that BRAF V600E and TERT promoter mutation is significantly correlated with the poor curative effect of RAI therapy in PTC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ChiCTR1800018760.

Could Urinary Iodine Be an Effective Predictive Factor for Thyroid Cancer After High Dose Radioactive Iodine Therapy?

OBJECTIVE: The study aimed to investigate whether urinary iodine concentration (UIC) and urinary iodine to creatinine ratio (UICR) measurements can act as markers for the curative effect of radioactive iodine (RAI) therapy. METHODS: A total of 337 patients who underwent RAI therapy between May 2018 and March 2020 were recruited. According to the levels of UIC or UICR, patients were divided into 6 groups: group A, UIC levels of <100 µg/L; group B, UIC levels ranging from 100 to 200 µg/L; group C, UIC levels of ≥200 µg/L; group D, UICR levels of <100 µg/g; group E, UICR levels ranging from 100 to 200 µg/g; and group F, UICR levels of ≥200 µg/g. Treatment and follow-up were defined according to the criteria used in the 2015 ATA guidelines. RESULTS: When dividing the 337 patients into 3 groups according to UIC levels, 50.7%, 22.6%, and 26.7% of patients were in the A, B, and C groups, respectively. Based on the UICR levels, 58.1%, 29.4%, and 12.5% of patients were in the D, E, and F groups, respectively. There was a significant positive correlation between UIC and UICR levels and iodine-131 uptake rates (P < .001). The excellent response rate was not significantly different between the UIC groups (P = .997) and the UICR groups (P = .634). In logistic regression analysis, UIC and UICR levels were not confirmed to be independent factors predicting the excellent response status, but an age of ≥55 years (OR = 0.373; P = .007) and Tg levels of ≥10 ng/mL (OR = 18.972; P = .001) were confirmed to be independent factors predicting the excellent response status at the end of follow-up. CONCLUSION: The UIC or UICR levels before RAI therapy did not compromise the therapeutic response to iodine-131.

Lymph node metastases >5 and metastatic lymph node ratio >0.30 of differentiated thyroid cancer predict response to radioactive iodine.

PURPOSE: The study was designed to elucidate the predictive value of the number of lymph node metastases (LNMs) and lymph node ratio (LNR) for response to therapy restratification system (RTRS). METHODS: From December 2015 to December 2019, 1228 patients who accepted radioactive iodine (RAI) were collected in the study. After 6-8 months, response to RAI was evaluated as complete response (excellent response) and incomplete response (indeterminate, biochemical, and structural incomplete response). The study developed classification tree to determine the optimum LNMs and LNR that predicted response to RAI. Multivariate logistic regression analyses were further analyzed to find independent factors of response to RAI. RESULT: The mean age of patients was 44 ± 12 and 71.09% (873/1228) were females. The best cutoff value of LNMs to affect RAI treatment response determined by classification tree was 5. Further in 388 patients with LNMs >5, the best cutoff value of LNR to affect RAI treatment response determined by classification tree was 0.30. With multivariate analysis, the study found that LNMs (>5), gender, lymph node dissection, and American Thyroid Association (ATA) risk classification were independent predictors of response to RAI for all 1228 patients; and LNR (>0.30), gender, and ATA risk classification for 388 patients with LNMs >5. The sensitivity analysis indicated that whether patients with LNM or not were included, the multivariate logistic regression model was kept stable. On subgroup analysis, no significant interactions were observed between the effect of LNMs/LNR and gender, N stage, ATA risk classification, lymph node dissection, or T stage. CONCLUSIONS: With classification tree, the study found that LNMs and LNR could predict initial response to RAI, and their optimal cutoff values were 5 and 0.30, separately.

Clinical Analysis of the Short-Term Outcome of Papillary Thyroid Micro Carcinoma After 131I Treatment.

PURPOSE: To explore the factors that influence the short-term clinical outcome after the first 131I treatment of papillary thyroid micro carcinoma (PTMC). PATIENTS AND METHODS: From October 2015 to June 2018, patients who were diagnosed with PTMC with lymph node metastasis were analyzed retrospectively, excluding patients with incomplete clinical data, distant metastasis, positive TGAb, TSH<30 mIU/L. The baseline data of sex, age, time from last surgery to first 131I treatment, tumor pathology information, and biochemical information were collected before admission. All patients included had radioactive iodine (RAI) with 3.70 GBq. The treatment response of patients was evaluated 6-8 months after discharge. By means of univariate and multivariate analysis, including excellent response (ER) and non-excellent response (NER) groups of clinical data, we assessed the impact of 131I on patients' outcome. A nomogram model was established based on the above independent risk factors. RESULTS: A total of 206 patients (59 males and 147 females, mean age 43.4 ± 10.6 years) were included in the study. The median follow-up time was 169.4 ± 10.5 days, including 139 patients in ER group (67.4%) and 67 patients in NER group (32.5%). Four factors including combining Hashimoto's thyroiditis, pre-ablative Tg levels, UIE levels, and lateral lymph node numbers were statistically different between ER group and NER group with significance at P < 0.05. Further multivariate analysis showed that Hashimoto's thyroiditis and Ps-Tg levels could be used as independent factors. The model verification showed that the C-index of the modeling set was 0.822, indicating that the nomogram model had a good predicted accuracy. CONCLUSION: Our data suggest that coexisting Hashimoto's thyroiditis and elevated Ps-Tg levels are predictive factors for short-term outcome of thyroid micro papillary carcinoma after 131I treatment. Also, the nomogram model had a good predicted accuracy.

Analysis of Curative Effect and Influencing Factors of N1 Stage Papillary Thyroid Micro-Carcinoma and Papillary Thyroid Non-Micro Carcinoma After Initial Radioactive Iodine Ablation Therapy.

OBJECTIVE: To compare the efficacy and influencing factors of initial radioactive iodine (RAI) ablation therapy for postoperative N1 stage papillary thyroid micro-carcinoma (PTMC) and papillary thyroid non-micro carcinoma (PTC), and to explore the necessity of RAI for N1 stage PTMC. METHODS: A retrospective analysis of patients with N1 stage papillary thyroid cancer who underwent RAI in our department from January 2018 to June 2019. According to the tumor diameter, papillary thyroid carcinoma was divided into PTMC group (≤ 1.0cm) with 129 patients and PTC group (> 1.0 cm) with 214 patients. According to the 2015 ATA guidelines, the patient's treatment response was evaluated 6-8 months after discharge from the hospital: excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), and structural incomplete response (SIR). IDR, BIR, and SIR were classified into NER group. Chi-squared test, independent sample t-test, Mann-Whitney U test, and binary logistic regression analysis were used to compare the differences between PTMC and PTC patients. RESULTS: The ps-Tg of the PTMC group was significantly lower than that of the PTC group (P = 0.001), and the ER ratio of the PTMC group was higher (χ2 = 5.445, P < 0.05). The ER ratio of PTMC patients in the N1a group was significantly higher than that of PTC patients (80%, 66.7%, χ2 = 4.076, P < 0.05), while the ER ratio of PTMC in the N1b group was not significantly different from that of PTC. Gender, N stage, and ps-Tg were found to be independent factors of RAI treatment response. CONCLUSION: The efficacy of the initial RAI of PTMC patients was significantly better than that of PTC patients. There was no significant difference in the efficacy of RAI between males with PTMC, N1b stage, ps-Tg ≥ 5.87ng/mL and PTC patients, which suggested that RAI is necessary for these patients.

A pre-ablative thyroid-stimulating hormone with 30-70 mIU/L achieves better response to initial radioiodine remnant ablation in differentiated thyroid carcinoma patients.

Our aim was to clarify the optimum pre-ablative thyroid-stimulating hormone (TSH) level for initial radioiodine remnant ablation (RRA) in patients with differentiated thyroid carcinoma (DTC). From December 2015 to May 2019, 689 patients undergone RRA at Nuclear Medicine Department, Second Hospital of Shandong University were included in the study. Patients were categorized by their pre-ablative TSH level grouping of < 30, 30-70 and ≥ 70 mIU/L. Response to RRA were evaluated as complete response (including excellent and indeterminate response) and incomplete response (including biochemical and structural incomplete response) after a follow-up of 6-8 months. Multivariable binary logistic regression model was used to explore the optimum pre-ablative TSH level range and independent factors associated with response to RRA. Rates of complete response to RRA were 63.04%, 74.59% and 66.41% in TSH level groups of < 30, 30-70 and ≥ 70 mIU/L, separately. With multivariate analysis, the study found that pre-ablative TSH levels, gender and lymph node dissection were independent predictors of response to RRA. TSH between 30 and 70 mIU/L had a higher rate of complete response compared with TSH < 30 mIU/L, OR 0.451 (95% CI 0.215-0.958, P = 0.036). A pre-ablative TSH level of 30-70 mIU/L was appropriate for patients with DTC to achieve a better response to RRA.

Analysis of the incidence and influencing factors of hyponatremia before 131I treatment of differentiated thyroid carcinoma.

BACKGROUND: Hyponatremia is a common clinical electrolyte disorder. However, the association between hyponatremia and acute hypothyroidism is unclear. Acute hypothyroidism is usually seen in patients who undergo preparation for radioactive iodine therapy. AIM: To analyze the incidence and influencing factors of hyponatremia in a condition of iatrogenic acute hypothyroidism in patients with differentiated thyroid cancer (DTC) before 131I treatment. METHODS: The study group consisted of 903 DTC patients who received 131I treatment. The clinical data before and after surgery, as well as on the day of 131I treatment were analyzed. According to the blood sodium level before 131I treatment, patients were divided into the non-hyponatremia group and hyponatremia group. Correlations between serum sodium levels before 131I treatment and baseline data were analyzed. Univariate analysis and binary logistic regression were performed to identify the influencing factors of hyponatremia. RESULTS: A total of 903 patients with DTC, including 283 (31.3%) males and 620 (68.7%) females, with an average age of 43.8 ± 12.7 years, were included in this study. The serum sodium levels before surgery and 131I treatment were 141.3 ± 2.3 and 140.5 ± 2.1 mmol/L, respectively (P = 0.001). However, the serum sodium levels in males and females before 131I treatment were lower than those before surgery. Patients aged more than 60 years and less than 60 years also showed decreased serum sodium levels before 131I treatment. In addition, the estimated glomerular filtration rate (eGFR) in males and females decreased before 131I treatment compared with those before surgery (P = 0.001). Moreover, eGFR in patients over 60 years and under 60 years decreased before 131I treatment, when compared with that before surgery. There were no significant differences in serum potassium, calcium, albumin, hemoglobin, and blood glucose in patients before surgery and 131I treatment (P > 0.05). Among the 903 patients, 23 (2.5%) were diagnosed with hyponatremia before 131I treatment, including 21 cases (91.3%) of mild hyponatremia and 2 cases (8.7%) of moderate hyponatremia. Clinical data showed that patients with mild hyponatremia had no specific clinical manifestations, while moderate hyponatremia cases were mainly characterized by fatigue and dizziness, which were similar to neurological symptoms caused by hypothyroidism and were difficult to distinguish. Correlation analysis showed a correlation between serum sodium before 131I treatment and the preoperative level (r = 0.395, P = 0.001). There was no significant correlation between blood sodium and thyroid-stimulating hormone (TSH) levels and urine iodine before 131I treatment (r = 0.045, P = 0.174; r = 0.013, P = 0.697). Univariate analysis showed that there were significant differences in age, sex, history of diuretic use, distant metastasis, preoperative blood sodium, blood urea nitrogen (BUN), eGFR, TSH and urinary iodine between the two groups (all P < 0.05). Logistic regression analysis showed that factors such as history of diuretic use, distant metastases, preoperative sodium and BUN were all influencing factors of hyponatremia. The Hosmer and Lemeshow test (c2 = 2.841, P = 0.944) suggested a high fit of the model. Omnibus tests of model coefficients indicated the overall significance of the model in this fitted model (P < 0.05). Preoperative serum sodium was a significant factor associated with pre-131I therapy hyponatremia (OR = 0.763; 95%CI: 0.627-0.928; P = 0.007). CONCLUSION: The incidence of hyponatremia induced by 131I treatment preparation was not high. Preparation for radioactive iodine therapy was not a risk factor for the development of hyponatremia in thyroid cancer patients.